Till Örebro universitet

Background and Aims: Plasma cholesterol (TC) and triglyceride (TG) levels are twice as high in hibernating brown bears (Ursus arctos) than in healthy humans. Yet, bears display no signs of atherosclerosis. To explore this apparent paradox, lipoprotein structure and function of brown bears were analyzed and compared with those of healthy humans.

Methods: Blood from the same wild free-ranging Swedish brown bears (n=10) was drawn during hibernation (winter) and active state (summer). Plasma lipoproteins were separated by size exclusion chromatography, ultracentrifugation and gel-electrophoresis. LDL binding to arterial proteoglycans (PGs) was measured. Data are presented as median (10th - 90th percentile).

Results: During hibernation bear LDL carried 4.6 (2.3-5.9) mmol/L cholesterol esters (CE), 1.5 (1.1-2.4) mmol/L unesterified (UC), 3.7 (2.1-4.9) mmol/L TG and 2.5 (1.8-3.4) mmol/L phospholipid (PL). Human LDL were smaller than bear LDL, which were proportionally richer in TG (winter 31 (26-33)%, summer 30 (22-40)%vs human 9% (7-15); p<0.001) and had less CE (winter 36 (26-45)%, summer 25 (21-37)%vs human 48 (46-55)%; p<0.01)). Bear LDL were less positively charged and showed a pre-ß motility on agarose gel. Thus, bear LDL had about 10 times lower binding to PGs than human LDL.

Conclusions: Despite high TC and TG levels, bear lipoproteins were less atherogenic than the human analogues. This was due to low LDL affinity for PGs, secondary to increased TG and PL, and to low positive charge. Our study provides further mechanistic insights for the atherosclerosis development, which is driven by the circulating lipoprotein composition and functions rather than plasma absolute lipid levels.